PT93633B - A process for the preparation of a bioactive composition comprising at least one derivative of ISOTIAZOLINONE or ISOTIAZOLOTIONA - Google Patents

Abstract

A composition comprises an isothiazolinone or an isothiazolothione and a substituted urea or a halogen-containing aromatic alkyl sulphoxide or sulphone. The isothiazolinone derivative can be 1,2-benzisothiazolin-3-one. The substituted urea may be 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The sulphoxide or sulphone may be a sulphone derivative such as di-iodomethyl-4-methylphenyl sulphone. A useful composition comprises 1,2-benzisothiazolin-3-one and the specified urea or sulphone derivative. The composition may include other materials including other compounds having anti-microbial properties.

Description

DESCRIPTION

The present invention relates to compositions that are used as industrial biocides.

Biocides are suitable for preventing industrial deterioration, in particular that caused by bacteria and fungi. Industrial biocides are used to conserve paints, latex, adhesives, skins, wood, metalworking fluids and cooling water.

A class of compounds that can be used as an industrial biocide is based on the isothiazolinone structure. Many descriptions of isothiazolinone derivatives have been made which are considered to have suitable biocidal properties. U.S. Patent 3761488 describes isothiazolinone derivatives in which alkyl, alkenyl,

- 1 r · * »* ι HTian ·>! ·!» ** ··· '*

alkynyl, cycloalkyl, aralkyl or aryl, which can optionally be substituted, are attached to the nitrogen atom and positions 4 and 5 are unsubstituted or are replaced with halogen or lower alkyl groups. U.S. Patent 3,571,022 describes benzisothiazolones in which a carbamoyl group is attached to the nitrogen atom and the benzene ring can be optionally substituted. North America Patent 3950349 describes N-thio substituted isothiazolin-3-one compounds that can be derived from isothiazolin-3-one or benisothiazolin-3-one. U.S. Patent 4165318 describes a solution of an isothiazolin-3-one in a polar organic solvent, wherein the solution also contains a stabilizing amount of formaldehyde British Patent Specification 2087388 describes 4,5-poly-methylene-4-isothiazolin- 3-one in which the polymethylene chain has three or four carbon atoms.

Another class of compounds that is considered to be fungicidal is based on the structure of isothiazolothione. British Patent Specification 1113634 describes compounds of this or an isomeric form, in which positions 4 and 5 are unsubstituted or can be substituted with alkyl or aryl groups or which can form a part of another ring system.

Isothiazolin-3-one that are unsubstituted on the nitrogen atom are capable of forming salts, for example with alkali metals such as sodium and potassium, and with ammonia or amines such as tri-ethanol-amine. These salts are generally soluble in water. British Patent Specification 1191253 describes and claims high strength aqueous solutions of crude 1,2-benzisothiazolin-3-one, in the form of a mixture of two or more of its different amine salts, the amines being selected from di-ethanol -amine, tri-ethanol-amine, diisopropanol-amine, triisopropanol-amine and morpholine. British Patent Specification 1330531 describes 1,2-benzisothiazolin-3-one compositions in aliphatic, cycloaliphatic or hetero-cyclic amines containing 2 to 6 carbon atoms and which are free of hydroxyl and ether groups. The Patent Specification

British 2004747 describes solutions of a 1,2-benzisothiazolin-3-one alkali metal salt in a hydroxyl organic solvent such as propylene glycol, dipropylene glycol and polyethylene glycols.

Such salt solutions do, however, require the addition of considerable amounts of extra organic solvent, for example glycols, to be sufficiently stable or commercially acceptable.

Compounds and compositions of the above types and related compounds of the same general type are effective to a varying degree, according to the particular compound or composition, against a range of bacteria and / or fungi. However, to reduce the cost of using these compounds, it is desirable to improve their effectiveness as anti-microbial materials.

Compositions have been proposed that contain more than one compound that has anti-microbial properties. In general, such compositions have an aggregate of the properties of the compounds present in the composition. Such compositions usually contain a compound that has suitable anti-bacterial properties in conjunction with a different compound that has suitable anti-fungal properties.

It was surprisingly found that certain compositions had suitable properties.

Thus, according to the present invention there is provided a composition that includes (a) at least one isothiazolinone derivative or at least one compound which is (b) at least one substituted urea, or (c) at least one alkyl sulfoxide or aromatic sulfone containing halogen.

The isothiazolinone or isothiazolothione derivatives that are component (a) of the composition are usually a compound of the general formula:

II

X

on what:

X represents an oxygen or sulfur atom;

R represents a hydrogen atom, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted hydrocarbyl group, a carbamoyl group or a cation;

A represents a hydrogen atom, a halogen atom, a cyano group, or a substituted or unsubstituted hydrocarbyl group;

D represents a hydrogen atom, a halogen atom, a cyano group, or a substituted or unsubstituted hydrocarbyl group; or

A and D, together with the carbon atoms to which they are attached, form a five or six membered ring, which can be optionally substituted.

Preferred component (a) is at least one isothiazolinone derivative, which is a compound in which X represents an oxygen atom. If the groups R, A and D are, or contain, substituted hydrocarbyl groups, the substituents are usually halogen, alkoxy or alkylthio, particularly those in which the alkyl groups contain 1 to 4 atoms. If R re'v. /

presents a carbamoyl group, it is of the general type -CONHrI where r! represents a hydrogen atom or a hydrocarbyl group, which can be substituted. It is generally preferred that the group R is a hydrogen atom or a lower alkyl group, which is an alkyl group containing 1 to 4 carbon atoms. R represents, in particular, hydrogen or a methyl group.

A and D can, together with the carbon atoms to which they are attached, form a 5- or 6-membered ring that can be substituted, the substituents being normally halogen, alkyl, alkoxy or alkylthio groups. The ring thus obtained may contain a hetero-atom, for example a nitrogen atom, but, in general, _A and D form a hydrocarbon ring such as a benzene, cyclopentene or cyclohexene ring. Alternatively, A and D represent separate groups and one or both of A and D may be a hydrogen atom. It is, in general, preferred that at least one of A and D is different from the hydrogen atom and is particularly a halogen atom, for example chlorine or a lower alkyl group.

Compounds that can be used as a component of the mixture include 2-methyl-isothiazolin-3-one (R represents methyl, A and D represent hydrogen); 5-chloro-2-methyl-isothiazolin-3-one (R represents methyl, A represents hydrogen and D represents chlorine); mixtures of the two previous compounds; 4,5-dichloro-e-methyl-isothiazolin-3-one (R represents methyl and A and D represent chlorine); 1,2-benzisothiazolin-3-one (R represents hydrogen and A and D form, together with the carbon atoms to which they are attached, a benzene ring); 4,5-tri-methylene-4-isothiazolin-3-one (R represents hydrogen and A and D form, together with the carbon atoms to which they are attached, a cyclopentene ring); and 2-methyl-4,5-trimethylene-4-isothiazolin-3-one (R represents methyl and A and D form, together with the carbon atoms to which they are attached, a cyclopentene ring).

In component (a), if R represents a cation, it may be a cation having a valence greater than one but is, in particular, a monovalent cation such as an alkali metal, amine or quaternary ammonium cation. As mentioned above, such materials are, in general, soluble in water and can thus be used in an aqueous medium.

Component (b) of the composition of the present invention is at least one substituted urea and is normally a urea that contains at least one substituent group on each nitrogen atom. A class of urea compounds that can be used contains a substituent group that is, or that contains, an aromatic group (an aromatic substituent) and in which no other substituent is attached to the nitrogen to which the aromatic substituent is attached. One or two substituents may be attached to the other nitrogen atom and these substituents are usually alkyl, alkenyl, alkynyl, alkoxy or cycloalkyl groups. Substituted ureas that can be used as component b are usually of the general formula:

Air 0 R ²

on what

Ar represents an aryl, substituted aryl, heterocyclic or substituted heterocyclic group;

R represents an alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, alkoxy or substituted alkoxy; and

- R represents a hydrogen atom or a group as defined 2 for R.

The substituted groups may contain one or more substituents selected from a hydrocarbon group,

a halogen atom, a hydro-carbonoxy group, a hydroxy group and an alkyl-amino-sulfonyl group or a mixture of such substituents.

Ar group can be an unsubstituted aryl group such as an unsubstituted aryl group such as a phenyl group, but generally contain at least one substituent which is a halogen atom, an alkyl group, an alkoxy group or a group aryloxy that can be replaced itself. Thus, the Ar group can be, for example, a phenyl, 4-chloro-phenyl, 3,4-dichloro-phenyl, 4-isopropyl-phenyl, 3-chloro-4-bromo-phenyl, 3-chloro-4 methyl-phenyl, 4- (4'-chlorophenoxy) phenyl or 4- ^{(1-methoxy-4-phenoxy)} phenyl. If the Ar group is or includes a heterocyclic group, it can be, for example, a benzothiazol-2-yl group or it can be a heterocyclic group having aromatic characteristics such as a pyridyl group.

3R and R groups are normally not substituted. In general R and R each do not contain more than six carbon atoms, in particular not more than four „atoms. 2 3 hydrogen, the groups R and R can be the same or different. 3

Normally R represents a hydrogen atom or a methyl group. The group R can be, for example, a methyl, n-butyl, methoxy, 2-methyl-cyclohexyl or 3-butyl group.

Substituted ureas that can be used with component (b) include

3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea,

3- (3,4-di-chloro-phenyl) -1-methyl-1-n-butyl-urea,

3- (3-chloro-4-bromo-phenyl) -1-methyl-1-methoxy-urea,

3- [4- (4'-chloro-phenoxy) phenyl] -1,1-di-methyl-urea,

3-14- (4'-methoxy-phenoxy) phenyl] -1,1-di-methyl-urea,

3- (4-chloro-phenyl) -1-methyl-1- (3-butanyl) -urea,

3-phenyl-1- (2-methyl-cyclohexyl) -urea, and

3- (benzothiazol-2-yl) -1-methyl-urea.

The other substituted ureas include

3- (4-isopropyl-phenyl) -1,1-di-methyl-urea,

3- (3,4-di-chloro-phenyl) -1-methyl-1-methoxy-urea,

3- (3-chloro-4-methyl-phenyl) -1,1-di-methyl-urea,

1.1- di-methyl-3-phenyl-urea,

3- (4-chloro-phenyl) -1,1-di-methyl-urea,

3- (3-chloro-4-methoxy-phenyl) -1,1-di-methyl-urea,

1.1- di-methyl-3- (3-tri-fluoro-methyl-phenyl) -urea,

3- (3-tert-butyl-carbamoyl-oxy) -phenyl-1,1-di-methyl-urea,

1.1- di-methyl-3- (4-tri-fluoro-methyl-phenyl) urea,

3- [3-chloro-4- (chloro-di-fluoro-methyl-thio) phenyl] -1,1-di-methyl-urea,

3- (3- [1 ', 1', 2 ', 2'-tetra-fluoro-ethoxy] phenyl) -1,1-di-methyl-urea, and 3- (3-chloro-4-tri-fluoro -methoxy-phenyl) -1,1-di-methyl-urea.

Compositions having suitable properties have been obtained in which component (b) is 3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea.

Substituted ureas that can be used as component (b) can be prepared by known procedures, for example, as described in British Patents 691403 and 692589 and United States Patents 2655455 and 2768971.

Materials suitable for use as component (c) have the general formula

4

Air SO R x

on what

Ar ¹ represents aryl, substituted, heterocyclic or substituted heterocyclic group;

R represents an alkyl, substituted alkyl, aryl or substituted aryl group;

x has a value of one or two; and at least one of the groups Ar and R contains at least one halogen substituent.

Substituents that may be present in

4 Ar and R groups include at least one halogen atom, hydrocarbyl group or hydrocarbiloxy group. Ar · * · or R ^, or both, contain at least one halogen atom substituent.

In a class of compounds that can be used as component (c), Ar ^ represents a heterocyclic group, in particular a substituted heterocyclic group having aromatic characteristics such as a pyridine ring that contains at least one halogen substituent, in particular, by minus two halogen atoms, for example, three halogen atoms. In such a compound it is preferred that R represents an unsubstituted alkyl group containing 1 to 12 carbon atoms.

Compounds of this type and the preparation of such compounds are described in more detail in British Patent 1103606, and in US Patents 3296272 and 3371011. As described in more detail in the aforementioned patents, compounds of this type can be prepared by oxidation of the corresponding thiopyridine compound. Suitable compounds of this type include those in which Ar '*' represents a pyridine ring containing three 4 or four halogen substituents, R represents a lower alkyl group, which is an alkyl group containing a maximum of six carbon atoms , and the value of x is two.

Compounds of this type include

2.3.5.6- tetra-chloro-4- (methyl-sulfonyl) -pyridine;

2.3.6- tri-chloro-4- (methyl-sulfonyl) -pyridine and

2.3.5.6- tetra-chloro-4- (isopropyl-sulfonyl) -pyridine.

In another class of compounds that can be used as component (c), Ar ¹ contains an aryl group, represents a methyl group substituted with halogen and ex has a value of two. Compounds of this general type, and their preparations, are described in more detail in U.S. Patents 3632859 and 3663623. As described in U.S. Patent 3632859, compounds of this type can be prepared by halogenating a sulfonyl acetic acid using for example sodium hypoiodide in sodium hydroxide solution.

The procedure of US Patent 3663623 is different in the halogenation phase that is carried out using iodine mono-chloride in an essentially neutral solution. Suitable compounds of this type include those in which Ar ¹ represents an aryl group substituted as alkyl, such as a 4-methyl-phenyl group and R represents a diiodine-methyl group.

Compositions having suitable properties have been obtained in which component (c) is diiodine-methyl-4-methyl-phenyl-sulfone.

As a particular embodiment of the present invention there is provided a composition consisting of (a) 1-2-benzisothiazolin-3-one with 3- (3,4-di-chloro-phenyl) -1,1-di-methyl -urea or with diiodine-methyl-4-methyl-phenyl-sulfone.

For convenience, hereinafter, the term the other component is used in relation to component (b) or component (c) or mixture of components (b) and (c).

The relative proportions of the components of the position can vary and compositions having suitable properties can be obtained which contain from 1% by weight of component (a) or the other component and, correspondingly, up to 99% by weight of the other component or of component (a). Preferred proportions depend on the compounds used as component (a) and the other component, and also on the particular system in which the mixture is to be used. In general, the composition contains at least 2% by weight of each component and, in particular, at least 8% by weight of each component.

The compositions of the present invention have anti-microbial properties. The compositions according to the present invention have been found to be active against bacteria and fungi. In addition, the compositions according to the present invention are such that the sum of the fractional inhibitory concentration (FIC) for all components of the composition is less than one and in the preferred compositions it is less than 0.7.

Especially preferred compositions are those in which the sum of the FIC for all components of the composition is not more than 0.6. The FIC is the ratio between the concentration of an individual component and the minimum inhibitory concentration of that component. It should be considered that if the sum of the FIC for all components of the composition is less than one, the composition is synergistic, the extent of the synergy being indicated by the amount in which the sum of the FIC is less than one. It has been found that some compositions according to the present invention are such that the sum of the FIC can be less than 0.6.

The compositions of the present invention have anti-microbial properties and are suitable for use as industrial biocides.

The compositions of the present invention provide good preservation in the wet state and can thus be used as a preservative for cutting fluids and also in cooling water applications. The conservation of wood and skins is another scope of application of the compositions. The compositions of the present invention can also be incorporated in paints as fungicides, in paint films that can be used without the addition of a bactericide.

The materials that are component (a) and the other component of the composition of the present invention are soluble in many polar solvents, although the solubility depends on the nature of the particular compounds that are present in the composition. However, many of the compounds are soluble in water, alcohols, ethers, ketones and other polar solvents or mixtures thereof.

The compositions of the present invention can be used alone as an anti-microbial material, but they can also be used in or in a suitable carrier material.

Thus, with another aspect of the present invention, a biocidal composition consisting of a

vehicle and an effective amount of a component composition (a) together with a component (b) or component (c) or with the two components (b) and (c) according to the present invention vehicle is normally a material that shows little, if any, anti-microbial activity and can be, or include, a material that is susceptible to the growth of microorganisms, in particular fungi. The vehicle can be a liquid medium and the biocidal composition can be a solution, suspension or emulsion of the composition of component (a) and the other component in a liquid vehicle. The vehicle can be water, in which one or both components (a) and the other component are essentially insoluble, or it can be a liquid such as acetic acid, N, N-di-methyl-formamide, propylene glycol, di-methyl -sulfoxide or N-methyl-2-pyrrolidone in which at least one, and preferably both, of component (a) and the other component are soluble. Alternatively, a mixture of liquids may be used, one being a solvent for component (a) and the other component and the other being non-solvent for the two components, and using such a mixture the composition normally consists , in an emulsion or drops of a solution of component (a) and the other component in the solvent dispersed in the non-solvent. If a suspension or emulsion is used, it conveniently contains a surfactant that is effective in maintaining the non-continuous phase as a suspension or emulsion. Any surfactant that is effective as a dispersant or emulsifier and known for use in biocidal compositions such as, for example, alkylene oxide copolymers, and alkylene oxide adducts of fatty alcohols, alkyl phenols and amines can be used. such as ethylene-di-amine. Other surfactants that can be used include sodium hydrogen sulfide, EO / PO / EO block copolymers, ethylene oxide condensates with nonyl-phenol or beta-naphthol, PO / EO copolymer condensates with non-phenol or ethylene -di-amine and condensates of naphthalene beta-sulfonic acid and formaldehyde. The surfactant is normally present in an amount comprised between 0.1 and 20% by weight of the total dispersion or emulsion weight in which the surfactant is active.

vo is incorporated. The dispersion or emulsion may include, in addition to the surfactant, other components that are known for inclusion in biocidal compositions such as thickening agents. Materials that can be used as thickening agents include polysaccharides, xanthine gum, sodium magnesium silicate, hetero-polysaccharides, alginates, carboxymethylcellulose, gum arabic, poly-acrylic acid and polyvinyl alcohol

Alternatively or in addition, the composition may include one or more solid components, which can act as vehicles or diluents. Solid materials that can be used as the optional component include inorganic materials such as metal oxides or their mixtures or compounds, for example aluminum oxide, silicon oxide, titanium dioxide, zinc oxide, talc, pyrophyllite, plaster , kieselguhr, chalk, diatomaceous earth, bentonite and filler earth and organic materials such as wheat flour, soy flour, wood flour, nutshell flour and lignin. The solid material is preferably in a finely divided form and normally has an average particle size of not more than 4 µm. Any optional solid can be added to the composition in an amount between 1% and a maximum of 99% by weight of the total weight of the most optional solid composition, and in general, the optional solid is present in an amount of at least 10% and not more than 80% by weight of the composition.

The composition can include an anti-dust agent, particularly if the composition is in a solid form. Suitable anti-dust agents include dodecyl benzene, tri-decyl octadecanoate, tri-methylol propane tri-dodecanoate, twitchell oil, Ensitol USN and mineral oil.

The amount of the composition that is present in the biocidal composition may be sufficient to have an anti-microbial effect or the composition may be present in an essentially greater proportion. It is to be considered that the biocidal composition can be provided as a solution, emulsion or dis

concentrated person which subsequently dilutes for use as an anti-microbial material. Thus, the amount of the composition of component (a) and the other component that is present in the biocidal composition is normally comprised between 0.0001% by weight of the biocidal composition.

The composition of the present invention is especially effective in providing antibacterial activity. Thus, the compositions can be used for the treatment of various means to inhibit the growth of microorganisms.

As another aspect of the present invention, a method is provided to inhibit the growth of microorganisms on or in a medium, which consists of treating the medium with a composition of component (a) and the other component as defined above.

The composition can be used in conditions where microorganisms, especially bacteria, grow and cause problems. Systems where microorganisms cause problems include liquid systems, particularly aqueous ones, systems such as cooling water liquors, metal working fluids, geological drilling lubricants, polymer emulations and surface coating compositions such as paints, varnishes and lacquers and also solid materials such as wood and leather. The composition of the present invention can be included in such materials to provide anti-microbial properties. Compositions that include component (c) can be incorporated into paints, varnishes or lacquers which can provide fungicidal characteristics.

As a particular aspect of the present invention there is provided a surface coating composition which contains an effective amount of a composition according to the present invention in which the composition includes component (c).

The composition of surface coating po14

to be a paint, varnish or lacquer and is, in particular, a paint, for example an emulsion paint. The amount of the composition which is present in the surface coating composition is normally between 0.001 and 2% by weight, and in particular between 0.1 and 1% by weight, relative to the total weight of the surface coating composition. The composition including component (c) provides fungicidal properties to the surface coating composition.

Component (a) and the other component of the composition of the present invention can be the only anti-microbial compound or can be used in conjunction with other compounds having anti-microbial characteristics. The composition can contain more than one compound which is component (a) and / or it can contain more than one material which is the other component. Alternatively, a composition of component (a) and the other component according to the present invention can be used in conjunction with one or more known anti-microbial compounds. The use of a mixture of antimicrobial compounds can provide a composition having a broader anti-microbial spectrum and thus a composition that is, in general, more effective than its components. The known anti-microbial compound can be one that has anti-bacterial, anti-fungal, anti-algae or other anti-microbial characteristics. The mixture of the composition of the present invention with other antimicrobial compounds normally contains from 1 to 99% by weight, relative to the weight of the total antimicrobial active compounds, the composition of component (a) and the other component, and particularly from 40 to 60% by weight of the composition of component (a) and the other component.

In unpublished, British pending patent application No. 8811948.2, now published as European Patent Application No. 345955, a composition is described that includes a halogenated aromatic di-nitrile, a substituted urea (as in component (b) composition of the present invention) and an aromatic alkyl sulfoxide or sulfone containing halogen (as in

component (c) of the composition of the present invention).

Preferred compositions according to said published European Patent Application have suitable anti-fungal and anti-algae activity. It has been found that the activity of these compositions can be increased if they are used in conjunction with the isothiazolinone derivative or the iso thiazolothione derivative which is component (a) of the composition of the present invention.

Thus, another aspect of the present invention provides a composition of component (a), component (b) and component (c) together with (d) at least one halogenated aromatic di-nitrile.

component (d) can be a phthalo-nitrile, an iso-phthalo-nitrile or a terephthalo-nitrile. The material suitable for use as component (d) has the general formula:

wherein each Y, which may be the same or different, represents a halogen atom; and n has a value from one to four.

When the value of n is less than four, the remaining oms in the aromatic ring are hydrogen atoms. Adequate results were obtained with the value of n four. Each group Y preferably represents a chlorine or fluorine atom. Conveniently, all Y groups are the same. The compounds that can be used as component (d) of the composition of the present invention are described in United States Patents 3290353 and 3331735. As described in more detail in United States Patent 3290353, compounds that can be used with

The component (d) can be prepared by reacting the corresponding acid halide, particularly acid chloride, with ammonia to provide the corresponding amide which then reacts with a dehydrating agent such as phosphorus pentoxide. The above procedure is suitable for the preparation of the chlorinated aromatic di-nitrile from which the fluorinated analog can be prepared by a halogen exchange reaction.

Compounds that can be used as component (d) of the composition of the present invention include tetra-chloro-isophthalo-nitrile; tetra-fluoro-isophthalo-nitrile and tetra-chloro-terephthalo-nitrile. Compositions having suitable properties have been obtained in which component (d) is tetra-chloro-isophthalo-nitrile.

As examples of other anti-microbial compounds that can be used together with the compositions according to various aspects of the present invention, mention can be made of quaternary ammonium compounds such as di-ethyl-dodecyl-ammonium chloride; di-methyl-octadecyl (di-methyl-benzyl) ammonium chloride; di-methyl-dodecyl-ammonium chloride; di-methyl-didodecyl-ammonium chloride; tri-methyl-tetradecyl-ammonium chloride; benzyl-di-methyl- (alkyl (C. _O -C _no )) ammonium chloride; cio1Z di-chloro-benzyl-di-methyl-dodecyl-ammonium rectum; hexadecyl-pyridine chloride; hexadecyl-pyridine bromide; hexadecyl-tri-methyl-ammonium bromide; dodecyl-pyridine chloride; dodecylpyridine bisulfate; benzyl-dodecyl-bis- (beta-hydroxy-ethyl) -ammonium chloride; dodecyl-benzyl-tri-methyl-ammonium chloride; benzyl-di-methyl chloride ((C ₁₂ -C 6 alkyl)) - ammonium; dodecyl-di-methyl-ethyl-ammonium ethyl sulfate; dodecyl-di-methyl- (1-naphthyl-methyl) -ammonium chloride; hexadecyl-di-methyl-benzyl-ammonium chloride; dodecyl-di-methyl-benzyl-ammonium chloride and 1- (3-chloro-allyl) -3,5,7-tri-aza-1-azonium-adamantane chloride; hydantoin derivatives such as 1,3-bis (hydroxy-methyl) -5,5-di-methyl-hydantoin and 1- (hydroxy-methyl) -5,5-di-methyl-hydantoin; amino compounds such as 1,3-bis (2-ethyl-hexyl) -5-methyl-5-amino-hexahydropyrimidine; hexa-methylene-tetra-ami

at; 1,3-bis (4-amino-phenoxy) -propane; and 2 - [(hydroxymethyl) -amino] ethanol; imidazole derivatives such as 1 [2- (2,4-dichloro-phenyl) -2- (2-propenyloxy) ethyl] -1H-imidazole; 2- (methoxy-carbonyl-amino) -benzimidazole; thio-cyanate derivatives such as methylene bis-thio-cyanate; tin compounds or complexes such as tri-butyl tin oxide, chloride, naphthoate, benzoate or 2-hydroxybenzoate; thiazole derivatives such as 2- (thio-cyano-methyl-thio) -benzothiazole; and mercapto-benzothiazole; nitro compounds such as tris (hydroxymethyl) nitro-methane; 5-bromo-5-nitro-1,3-dioxane and 2-bromo-2-nitro-propane-1,3-diol; aldehydes and derivatives such as gluteral-aldehyde (pentanediol); p-chloro-phenyl-3-iodo-propargyl-formaldehyde and glyoxal; amides such as chloracetamides; Ν, Ν-bis (hydroxymethyl) chloracetamide; N-hydroxy-methyl-chloracetamide and di-thio-2,2-bis (benzmethyl-amide); guanidine derivatives such as polyhexamethylene-biguanide and 1,6-hexa-methylene-bis [5- (4-chloro-phenyl) biguanide]; uncle such as

3,5-di-methyl-tetrahydro-1,2,5-2H-thio-diazine-2-thione; thiazine derivatives such as hexahydro-triazine and 1,3,5-tri- (hydroxy-ethyl) -1,3,5-hexahydro-triazine; oxazolidine and its derivatives such as bis-oxazolidine; furan and its derivatives such as 2,5-dihydro-2,5-di-alkoxy-2,5-di-alkyl-furan; carboxylic acids and their salts and esters such as sorbic acid and their salts and 4-hydroxybenzoic acid and their salts and esters and phenol and their derivatives such as 5-chloro-2- (2,4-dichloro-phenoxy) phenol; thio-bis (4-chloro-phenol) and 2-phenyl-phenol.

Various aspects of the present invention are described in the following illustrative examples.

In the following examples, the compositions according to the present invention were subjected to an evaluation of the anti-microbial properties of the compositions. The evaluation was carried out, under totally sterile conditions, as follows.

In the microbiological evaluation, several compositions were tested for anti-microbial activity against bacteria using Pseudomonas aeruginosa.

MICROBIOLOGICAL EVALUATION

The materials or mixtures of materials to be tested were added to a nutrient broth in quantities to provide the desired concentration of the added material. The addition materials were added in concentrations of zero to values above the minimum inhibition concentration of the particular material. In the mixtures, the concentrations of each material were varied in a systematic way to provide an array of mixtures of different relative proportions and different total concentrations.

The effect of inhibiting the growth of bacteria was investigated by inoculating each sample of the broth with sufficient amount of the test bacterium to provide approximately 10% cells in cm. The mixture was incubated at 30 ° C for 24 hours. At the end of the test period, the presence of turbidity in the broth indicated that the test substance had grown. The lack of turbidity indicated that there had been no growth. The lowest concentration of material or mixture was registered, which stopped all growth. The results were used to plot an isobologram from which the sum of the fractional inhibitory concentration for a mixture can be determined.

EXAMPLE 1

The microbiological evaluation, as described, was performed using the bacterium Pseudomonas alruginosa. The tested composition was a mixture of 1,2-benzisothiazolin-3-one and 2,3,5,6-tetra-chloro-4- (methyl-sulfonyl) -pyridine.

The concentrations of 1,2-benzisothiazolin-3-one. . —3 used were 0.5,11,16,22,28,33,39,44 and 50 micrograms cm. 2,3,5,6-tetra-chloro-4- (methyl-sulfonyl) -pyridine in concentrations of 0, 14, 28, 42, 56, 69, 83, 97, 111 and 125 mi-3 were used cm

From the results obtained, the lowest sum of FIC was 0.72 which was achieved with a mixture containing -3 of 11 micrograms cm of 1,2-benzisothiazolin-3-one and 28 micro-3 grams.cm of 2 , 3,5,6-tetra-chloro-4- (methyl-sulfonyl-pyridine. Details of the mixtures used and the results obtained are shown in Table One.

TABLE ONE

1 Mixtures 1 1 BIT (a) TCSP (b). FIC I (ppm) 1 1 (ppm) 1 1 1 1 I 11 1 1 28 0.72 1 1 11 1 42 ¹ 0.84 l 1 11 I ⁵⁵ 1 0.94 1 1 L 16 1 14 1 0.84 1

Table Notes One (a) BIT (b) TCSP represents 1,2-benzisothiazolin-3-one.

represents 2,3,5,6-tetra-chloro-4- (methyl-sulfonyl) -pyridine.

EXAMPLE 2

The procedure of Example 1 was repeated with the exception that 2,3,5,6-tetra-chloro-4- (methylsulfonyl) pyridine was replaced with diiodine-methyl-4-methyl-phenylsulfone.

The concentrations of 1,2-benzisothiazolin-3-one used were 0, 5, 11, 16, 22, 28, 33, 39, 44 and 50 microgra-3 mas.cm

Diiodo-methyl-4-methyl-phenyl-sulfo20 was used

at the concentration of 0, 55, 111, 166, 221, 277, 332, 388, 444 and -3

500 micrograms.cm

From the results obtained, the lowest sum of FIC was 0.56, which was achieved with a mixture containing 11 micrograms.cm of 1,2-benzisothiazolin-3-one and 111 mi-3 crograms.cm in diameter. iodo-methyl-4-methyl-phenyl-sulfone. Details of the mixtures used and the results obtained are shown in Table Two.

TABLE TWO

1 Mixtures 1 1 FIC 1 1 BIT (a) | (ppm) 1 DIMS (c) 1 | (PPm) | 1 5 1 277 ' 1 0.71 1 11 | 111 ¹ 0.56 ¹ 1 ¹¹ ! 166 1 0.83 | 11 221 0.94 1 16 1 1 55 1 1 1 0.6 ¹ 1

Notes to Table Two (a) is as defined in the Notes to Table One.

(b) DIMS represents diiodine-methyl-4-methyl-phenyl-sulfone.

EXAMPLE 3

The procedure of Example 1 was repeated, with the exception that 2,3,5,6-tetra-chloro-4- (methyl-sulfonyl) -pyridine was replaced by 3- (3,4-dichloro-phenyl) ) -1,1-di-methyl-urea.

1,2-Benzisothiazolin-3-one concentrations

used were 0, 5, 11, 16, 22, 28, 33, 39, 44 and 50 micro -3 grams.cm

3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea was used at concentrations of 0, 55, 111, 166, 221, 277, 332, _3

388, 444 and 500 micrograms.cm

From the results obtained, the lowest sum of FIC was 0.56 which was achieved with a con-3 mixture having 5 micrograms.cm of 1,2-benzisothiazolin-3-one and 166 mi -3 crograms.cm 3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea. Details of the mixtures used and the results obtained are shown in Table Three.

TABLE THREE

Mixtures

1 BIT (a) I DCDMU (d) | (ppm), FIC | 1 1 (ppm), 1 1 5 1 1 1 166 | 0.56 Γ 1 I 11 | ¹¹¹ 1 0.72 I 1 16 1 1 55 1 0.84 1 1

Notes to Table three (a) is as defined in the Notes to Table One.

(b) DCDMU represents 3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea.

EXAMPLE 4

The procedure of Example 1 was repeated with the exception that 2,3,5,6-tetra-chloro-4- (methyl-sulfonyl) -pyridine was replaced by a mixed biocide composition possessing

a composition of 40% by weight of tetra-chloro-iso-phthalonitrile, 40% by weight of 2,3,5,6-tetra-chloro-4- (methylsulfonyl) -pyridine and 20% by weight 3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea.

The biocidal composition was prepared by mixing the components together by grinding in a mortar and pestle.

The concentrations of 1,2-benzisothiazolin-3-one used were 0, 5, 11, 16, 22, 28, 33, 39, 44 and 50 micro-3 grams.cm. The mixed biocide was used in concentrations of 0, 55, 111, 167, 222, 278, 333, 389, 444 and 500 micrograms. -3 cm, the weights being the weight of the biocidal composition so mixed.

From the results obtained, the lowest sum of FIC was 0.63 which was achieved with a con-3 mixture having 16 micrograms.cm of 1,2-benzisothiazolin-3-one and 55 mi. mixed. Details of the mixtures used and the results obtained are shown in Table Four.

TABLE FOUR

| Mixtures 1 | BIT (a) | MBC-1 (e) | FIC l (ppm) | (ppm), 1 1 16 | I 1 55 0.63 ¹ 16 ¹ 111 ' 0.77 1 ιθ 1 167 | 0.91 1 ²² 1 ⁵⁵ 1 0.81

Notes to Table Four (a) is as defined in the Notes to Table One.

(b) MBC-1 represents the mixed biocidal composition described in Example 4.

EXAMPLE 5

The procedure of Example 4 was repeated, using a mixed biocidal composition prepared in the same manner but having a different composition, namely 30% by weight of tetra-chloro-iso-phthalonitrile, 30% by weight of 2.3.5, 6 -tetra-chloro-4- (methyl-sulfonyl-phenyl) -pyridine, 20% by weight of 3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea and 20% by weight of zinc oxide.

The concentrations of 1,2-benzisothiazolin-3-one used were 0, 5, 11, 16, 22, 28, 33, 39, 44 and 50 micro-3. .

grams.cm. The mixed biocide was used at concentrations of 0, 28, 55, 83, 111, 139, 166, 194, 222 and 250 micrograms.cm with the weights being the weight of the total mixed biocidal composition including zinc oxide.

From the results obtained, the lowest sum of FIC was 0.57 which was achieved with a mixture containing 11 micrograms.cm of 1,2-benzisothiazolin-3-one and 111 micro -3 grams.cm of the divided composition mixed. The details of the mixtures used and the results obtained are shown in Table five.

TABLE FIVE

Mixtures | FIC BIT (a) j (ppm) I MBC-2 (f) | (ppm) ι 1 n | 1 111 0.57 ¹⁶ 1 28 ' 0.89

Notes to Table Five (a) is as defined in the Notes to Table One (f) MBC-2 represents the mixed biocidal composition described in Example 5.

EXAMPLE 6

The procedure of Example 4 was repeated, using a mixed biocidal composition prepared in the same manner but having a different composition, namely 55% by weight of tetra-chloro-iso-phthalonitrile, 20% by weight of diiodine-methyl- 4-methyl-phenyl-sulfone and 25% by weight of 3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea.

The concentrations of 1,2-benzisothiazolin-3-one used were 0, 5, 11, 16, 22, 28, 33, 44 and 50 micrograms.cm. The mixed biocide was used in concentrations of 0, 28, 55, 84, 111, 139, 166, 194, 222 and 250 micrograms.cm \ with weights being the weight of the total mixed biocidal composition.

From the results obtained, the lowest sum of FIC was 0.58 which was achieved with a con-3 mixture having 11 micrograms.cm of 1,2-benzisothiazolin-3-one and 55 mi. mixed. Details of the mixtures used and the results obtained are shown in Table Six.

TABLE SIX

| Mixtures | FIC | BIT (a) | (ppm) | MBC-3 (g) | (ppm), 1 ⁵ | 1 166 ι 0.90 11 1 1 55 1 0.58

11 ¹ 83 ¹ 0.71 11 1 139 | 0.96 ¹⁶ 1 1 ²⁸ 1 | 0.61 22 28 0.79

Notes to Table six (a) is as defined in the Notes to Table One.

(g) MBC-3 represents the mixed biocidal composition described in Example 6.

EXAMPLE 7

The procedure of Example 4 was repeated, using a mixed biocidal composition prepared in the same way but having a different composition, namely 35% by weight of tetra-chloro-iso-phthalonitrile, 20% by weight of diiodine-methyl- 4-methyl-phenyl-sulfone, 25% by weight of 3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea and 20% by weight of zinc oxide.

The concentrations of 1,2-benzoisothiazolin-3-one used were 0, 5, 11, 16, 22, 28, 33, 39, 44 and 50 mi-3 crograms.cm. The mixed biocide was used in concentrations of 0, 28, 55, 83, 111, 139, 166, 194, 222 and 250 microgra-3 mas.cm, the weights being the weight of the total mixed biocidal composition including zinc oxide .

From the results obtained, the lowest sum of FIC was 0.77, which was achieved with a con-3 mixture having 16 micrograms.cm of 1,2-benzisothiazolin-3-one and 28 ml. mixed biocide. Details of the mixtures used and the results obtained are shown in Table Seven.

TABLE SEVEN

| Mixtures | FIC 1 BIT (a) ’ (ppm) | I MBC-4 (h) ' (ppm) | I 1 5 | 1 111 | 0.98 ¹¹ 1 ⁸³ 1 0.99 16 1 55 0.97 16 ¹ L 28 ¹ 1 0.77

Notes to Table Seven (a) is as defined in the notes to Table One.

(h) MBC-4 represents the mixed biocidal composition described in Example 7.

EXAMPLE 8

The procedure of Example 5 was repeated, with the exception that 1,2-benzisothiazolin-3-one was replaced by

2-methyl-4,5-tri-methylene-4-isothiazolin-3-one.

The concentrations of 2-methyl-4,5-tri-methylene-4-isothiazolin-3-one used were 0, 5, 11, 16, 22, 28, 33, -3

39, 44 and 50 micrograms.cm. The mixed biocide was used at concentrations of 0, 14, 28, 55, 83, 111, 139, 166, 194, 222 and -3

250 micrograms.cm, with weights being the weight of the total mixed biocidal composition, including zinc oxide.

From the results obtained, the lowest sum of FIC was 0.51 which was achieved with a mixture containing -3 micrograms.cm of 2-methyl-4,5-tri-methylene-4-isothiazolin-3-3

-one and 55 micrograms.cm of the mixed biocidal composition. The

details of the mixtures used and the results obtained are shown in Table Eight.

TABLE EIGHT

Mixtures FIC MTI (i) (ppm) MBC-2 (f) (ppm) 5 ₅₅ 0.51 11 28 0.56 16 14 0.65

Notes to Table Eight (f) is as defined in the Notes to Table Five.

(i) MTI represents 2-methyl-4,5-tri-methylene-4-isothiazolin-3-one

EXAMPLES 9 to 11

An aqueous dispersion was prepared by wet grinding 9% by weight of tetra-chloro-iso-phthalonitrile; 6% by weight of 3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea; 9 & by weight of 2,

3,5,6-tetra-chloro-4- (methyl-sulfonyl) -pyridine; 6% by weight of zinc oxide; 10% by weight of propylene glycol; 3% by weight of an ethylene oxide / propylene oxide / ethylene oxide block copolymer containing 44% by weight of ethylene oxide units and wherein the average molecular weight of the propylene oxide block is 2,700; and water up to 100% by weight.

The previous aqueous dispersion was mixed with an aqueous dispersion, with pH 6 to 8, containing 33% w / v 1,2-benzisothiazolin-3-one, by stirring the two dispersions together. The dispersions were mixed in different proportions, with 28

shown in Table Nine.

TABLE NINE

Mixture (parts by volume) (j) Example BD ND 9 1 10 10 1 15 11 1 20 -

Notes to Table Nine (j) BD. represents the aqueous dispersion containing 33% w / v 1,2-benzoisothiazolin-3-one.

ND represents the aqueous dispersion including tetra-chloro-nitrile, 3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea, 2,3,5,6-tetra-chloro-4- (methyl-sulfonyl) -pyridine and zinc oxide.

The mixing ratios are referred to the total volume of each aqueous dispersion.

EXAMPLES 12 to 20

The mixed dispersions of Examples 9 to 11 were added to aliquots of 50 grams of an acrylic emulsion paint for exteriors (based on Revacryl latex with pH 9) containing 0.2% yeast extract. The mixed dispersions were added to the ink in quantities to provide a level of 1,2, benzisothiazolin-3-one of 100, 200 or 300 ppm w / v in the ink. The ink mixture containing the added mixed dispersions was then inoculated with a mixture of the bacteria.

inoculum was a mixed suspension of bacteria that were prepared by mixing equal amounts of suspensions that each contained different bacteria from the hydrophilic Aeromonas, Proteus rettgeri, Pseudomonas aeruginosa, Serratia marcescens, Alcaligenes spp, Pseudomonas cepacia and Pseudomonas putida bacteria.

Each ink mixture was inoculated with 1 cm of mixed bacterial suspension and inoculated at 30 ° C. After contact times of one, three and seven days, a small aliquot of the paint mixture was removed and bacterial growth was examined. The extent of bacterial growth was recorded.

After removing the aliquot on the seventh day, an additional 3 cm of the mixed bacterial suspension was added. Aliquots were removed after one, three and seven days of the second week. At the end of the se. . Every second week, an additional 1 cm of the mixed bacterial suspension was added. Aliquots were removed after one, three and seven days of the third week. The results obtained are shown in Table Ten below.

For comparative purposes, additional paint mixtures were prepared which contained only the 1,2-benzisothiazolin-3-one dispersion or only the dispersion including tetra-chloro-iso-phthalonitrile; 3- (3,4-di-chloro-phenyl) -1,1-di-methyl-urea; 2,3,5,6-tetra-chloro-4- (methyl-sulfonyl) -pyridine and zinc oxide.

The results of the tests using these comparative ink mixes are also shown in Table Ten.

TABLE TEN

Ί 'Ex.  Disp (j) (k) 1 Bacterial growth Week 1 Week 2 Week 3 1 1 1 or With Ex Day | Day Day • Type J | (ppm) (D 1 | I ³ 1 I 7 I 1 j I ³ 1 1 7 1 | 1 3 1 7 1 1 12 1 ⁹ 1 | 300 1 0 1 1 the 1 the 1 1 the 1 Γ ο 1 0 r 2 | 0 1- 1st I 13 ί 9 | 200 ⁰ 1 ⁰ 1 ⁰ 1 ⁴ 1 ⁰ 1 0 4, 2 1st 14 9 I 100 I 1 3 1 1 0 1 4 1 3 1 1 4 4 1 4 1 15 ¹ 10 300 - 0 ' 0 ^{* 1 *} 0 1 the l the 1 0 1 ' 0 1 0 1 16 1 ¹⁰ | 200 the 1 the 1 the 1 ² 1 the 1 0 ³ 1 0 1st 1 17 1 io | yo 1 | ο 1 the 1 4 | the 1 0 4 | 3 1st | 18 1 n | 300 ο 1 ο 1 ο 1 the 1 the 1 0 0 | 0 1st 19 1 ii | 200 the 1 the 1 the 1 i | the 1 0 ² 1 0 1st 1 20 1 n | yo ί | the 1 ° 1 4 | the 1 0 4 | 0 1st 1 THE | BD | 300 the 1 the 1 the 1 ³ 1 ³ 1 3 ³ 1 3 1st 1 B 1 BD | 200 2 | ί | the 1 4 | ³ 1 1 4, 4 1 ³ 1 Ç 1 BD | yo 4 | ⁴ 1 ⁴ 1 ⁴ 1 4 | 4 nm | NM | nm 1 D 1 ND 1 2 * the 1 o | the 1 4 I ² 1 2 4 | 4 1 ⁴ 1 AND 1 ND 1 i * 4 | ⁴ 1 2 | 4 | 4 I 4 nm | NM | nm 1 F ND | 0.5 * 4 | 4 | ⁴ 1 ⁴ 1 ⁴ 1 4 nm | NM | nm 1 G | ND | 0.25 * 4 1 ⁴ 1 ⁴ 1 ⁴ 1 4 | 4 nm | NM | nm 1 H | NIL | NIL ⁴ 1 ⁴ 1 ⁴ 1 4 I 4 | 4 4 I 4 1 ⁴

Notes to Table Ten (j) is as defined in Notes to Table Nine (k) 9, 10 and 11 represent the dispersions of Examples 9, 10 and

11.

(l) The quantities are given as ppm w / v relative to the ink mixture of the 1,2-benzisothiazolin-3-one component of the aqueous dispersion.

* These quantities are given as a% w / v relative to the paint mixture of the total aqueous dispersion identifier as ND.

(m) 0 means no growth (colonies not visible).

it means a trace of visible growth.

means slight growth (some colonies visible).

means moderate growth (discrete colonies visible possibly with some coalescence).

means dense / confluent growth (fully visible coalescent colonies).

NM means measurements not taken since the previous results indicated there was no residual activity.

EXAMPLES 21 to 29

The procedure described for Examples 12 to 20 was repeated with the exception that the acrylic emulsion paint containing yeast extract was replaced by an aqueous emulsion paint formulation of polyvinyl acetate which did not contain yeast extract.

The results obtained are shown in the Table

Eleven to follow.

TABLE ELEVEN

1 Ex. | Disp (j) (k) Bacterial growth | Week 1 Week 2 Week 3 1 1 OR Day Day 1 Day | 1 With Ex J- ι Type ι (ppm) (D I 1 1 3 I 7 1 1 ³ I 1 7 I 1 1 1 3 7 1 1 1 ²¹ 1 ⁹ 1 I 300 1 o | O 0 1 ι 1 o ΊΤ- Ι ° 1 3 4 —1 ⁷ 1 | 22 1 ⁹ | 200 o | O 0 ³ 1 ³ 1 ⁴ 1 NM NM nm | | 23 1 ⁹ | 100 ι 1 o 1 4 I 4 | 4 | NM NM nm | 1 ²⁴ 1 ¹⁹ | 300 o | O 0 0 | 0 1 ° 1 2 3 ³ 1 1 ²⁵ 1 ¹⁰ | 200 o | O 0 0 | 0 1 ° 1 3 4 4 | | 26 1 ¹⁹ | yo o | O 0 2 | 2 1 ⁴ 1 4 4 ⁴ 1 | 27 1 ii | 300 o | O 0 0 | 0 I θ 1 0 0 ° 1 | 28 | ii | 200 o | O 0 0 | 0 1 ° 1 1 0 θ 1 | 29 1 ii | yo o | O 0 4 | 4 1 ⁴ 1 NM NM nm | | I | BD | 300 2 | 2 0 2 1 i 1 ⁴ 1 4 4 ⁴ 1 1 ^J 1 BD | 200 4 I 4 4 4 | 4 1 ⁴ 1 NM NM nm | ^1K 1 BD | yo 4 | 4 4 4 | 4 1 ⁴ 1 NM NM nm | 1 ^L 1 ND | 2* ³ 1 ⁴ 4 4 | 4 1 ⁴ 1 NM NM nm | | M | ND 1 1 * 4 | 4 4 4 | 4 1 ⁴ 1 NM NM nm | 1 ^N ND | 0.5 * 4 | 4 4 4 | 4 1 ⁴ 1 NM NM nm | 1 ⁰ | ND | 0.25 * 1 4 I 4 1 ⁴ 1 ⁴ 1 ⁴ 1 ⁴ 1 NM NM nm | 1 ^p | NIL 1 NIL 4 | 4 ^{4 4} I 4 1 ⁴ 1 4 4 4 I

Notes to Table Eleven (j) is as defined in the Notes to Table Nine.

k, 1 and m are all as defined in the Notes to Table Ten.

Claims (4)

CLAIMS - wool Process for the preparation of a biocidal composition characterized by incorporating a) to 99% by weight of at least one isothiazolinone derivative or at least one iso-thiazolothione derivative, and correspondingly 99 to 1% by weight of b) at least one substituted urea or c) at least one alkyl sulfoxide or aromatic sulfone containing the halogen or a mixture of b) and c). 2. A process according to claim 1, characterized in that a) it is at least one compound of the general formula: X wherein X is an oxygen or sulfur atom R is a hydrogen atom, an optionally substituted hydrocarbyl group, a group optionally substituted hydro-carbylthio, an optionally substituted hydro-carbyloxy group, a carbamoyl group or a cation; A is a hydrogen atom, a halogen atom, a cyano group, or an optionally substituted hydrocarbyl group; or A and D together with the carbon atoms to which they are attached form a pentagonal or hexagonal ring, which can be replaced. Process according to claim 2, characterized in that in component a) X is an oxygen atom; and R is a hydrogen atom, an alkyl group containing between 1 and 4 carbon atoms or a monovalent cation which is an alkali metal, an amine or a quaternary ammonium. The process according to claim 2 or 3, characterized in that A and D together with the carbon atoms to which they are attached form an optionally substituted pentagonal or hexagonal hydrocarbon ring. 5. A process according to any of claims 2 to 4, characterized in that component a) is selected from 2-methyl-iso-thiazolin-3-one; 5-chloro-e-methyl-iso-thiazolin-3-one; 4,5-dichloro-2-methyl-iso-thiazolin-3-one; 1,2-benzisothiazolin-3-one; 4,5-trimethylene-4-iso-thiazolin-3-one and 2-methyl35 -4,5-trimethylene-4-isothiazolin-3-one. 6. A process according to any one of claims 1 to 5, characterized in that the substituted urea which is with component b) is of the formula: Ar where Ar is an aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic or heterocyclic substituted 2 do; R is an alkyl, substituted alkyl, alkenyl, al3, substituted kenyl, alkoxy or substituted alkoxy group; and R and one,. 2 hydrogen atom or a group as defined for R. 7. A process according to claim 6, characterized in that the Ar group contains at least one substituent which is a halogen atom, an alkyl group, an alkoxy group or an aryloxy group and that the substituent group can be substituted by a selected substituent between the same group of substituents. Process according to claim 6 or 7, At least one of the groups Ar and R contains at least one halogen substituent. - 113 - Process according to claim 10, characterized in that Ar ^ is a pyridine ring containing at least 4 halogen substituents and R ser is an unsubstituted alkyl group containing between 1 and 12 carbon atoms or Ar ^ contains an aryl group, R being a halogen-substituted group and ex having a value of 2. Process according to claim 11, characterized in that component c) is 2,3,5,6-tetrachloro-4- (methylsulfonyl) pyridine; 2,3,6-trichloro-4- (methylsulfonyl) pyridine; 2,3,5,6-tetrachlor-4- (isopropyl-sulfonyl) pyridine or di-iodomethyl-4-methyl-phenyl-sulfone. 133. The method of claim 1, wherein the a) 1,2-benzisothiazolin-3-one is incorporated; and at least one compound that is b) 3- (3,4-dichlorophenyl) -1,1-dimethyl-urea; or c) di-iodomethyl-4-methyl-phenyl-sulfone. 143. Process according to any one of the preceding claims, characterized in that it additionally incorporates a component which is an antimicrobial compound which is at least one aromatic dinitrile halogenate of the general formula. CN where each Y, which can be the same or different, is a halogen atom; and n has a value between 1 to four. Process according to claim 4, characterized in that the dinitrile is tetrachloro-isophthalo-nitrile, tetra-fluoro-isophthalo-nitrile or tetrachloro-terephthalo-nitrile. 163. The method of claim 5, wherein 1,2-benzisothiazolin-3-one is incorporated; 3- (3, 2 3 characterized by R and R being unsubstituted and each containing a maximum of 6 carbon atoms. 93. The method of claim 6 to 8, wherein the substituted urea is 3- (benzothiazol-2-yl) -1-methyl-urea. Process according to claims 1 to 9, characterized in that at least one alkyl sulfoxide or aromatic sulfone incorporates a halogen of the general formula: Air SO R where 1, ^x Ar and an aryl, substituted aryl, hetero-aryl, substituted hetero-aryl, heterocyclic, substituted heterocyclic group; 4, R is an alkyl, substituted alkyl, aryl or substituted aryl group; x has the value of one or two; and 3-phenyl-1- (2-methyl-cyclo-hdxyl) urea, or 3- (4-chloro-phenyl) -1-methyl-1- (3-butynyl) -urea, 3- [4- (4 ¹ -methoxy-phenoxy) phenyl] -1,1-dimethyl-urea, 3- [4- (4 ¹ -chloro-phenoxy) phenyl] -1,1-dimethyl-urea, 3- (3-chloro-4-bromo-phenyl) -1-methyl-1-methoxy-urea, 3- (3,4-dichlorophenyl) -1-methyl-1-n-butyl-urea, 3- (3,4-dichloro-phenyl) -1,1-dimethyl-urea, 4-dichlorophenyl) -1,1-dimethylurea; di-iodomethyl-4-methyl-phenylsulfone and tetrachloro-isophthalonitrile. The applicant claims the priority of the British application submitted on March 31, 1989, under number 8907298.7.